This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Metals play an integral role in the function of many proteins. The structural determination of these metalloproteins is fundamental for elucidating the molecular mechanisms by which metals mediate their biological processes. This proposal focuses on structural studies of metalloenzymes in three major areas: (1) the structural determination of methanogenic proteins involved in generating the methyl group from acetate and methylamines, (2) the structural determination of novel metalloproteases, and (3) the structural determination of protein oxygen sensors. A number of proteins in each thrust area have been crystallized and projects are currently at various stages towards their structure solution. The focus of future studies will be to complete ongoing structural determinations using MAD and MIR data collected on SSRL beamlines and to determine the structures of inhibitor and intermediate complexes of these proteins to clarify issues related to mechanism and ligand binding.
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